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External volume expansion (EVE) is an effective method of adipose tissue regeneration. However, it remains unclear how EVE induces adipose tissue regeneration. In this study, we developed EVE devices to generate expanded prefabricated adipose tissue (EPAT) in rats and investigated cell proliferation, adipogenesis, and the expression of extracellular matrix (ECM) proteins during the 12 weeks suction. In addition, EPAT-generated decellularized adipose tissue (DAT) was used to assess the role of ECM proteins in cell proliferation and differentiation. Matrix deposition was significantly increased after EVE suction, with fibronectin and laminin showing the most dramatic changes. Fibronectin expression peaked during weeks 1-4, when Ki67 cells in EPAT peaked. Laminin expression peaked during weeks 8-12, when peroxisome proliferator-activated receptor-γ expression also peaked. In vitro , adipose-derived stem cells (ASCs) displayed a higher proliferation rate in week 1 DAT, when fibronectin expression was highest, whereas ASC adipogenesis was significantly higher on week 12 DAT, when laminin expression was abundant. These results showed that EVE device enhanced ECM deposition, which is closely related to cell proliferation and differentiation. Impact Statement Large soft tissue defects caused by cancer, trauma, or deformity remain a major challenge for reconstructive surgery. External volume expansion (EVE) successfully induces adipose tissue regeneration and shows great therapeutic potential in correction for soft tissue defect. This study showed that EVE enhanced the secretion of extracellular matrix (ECM) proteins and regulated ASC proliferation and differentiation through shifting matrix synthesis from fibronectin to laminin. These findings revealed the relation between ECM modulation and ASC behavior, indicating that EVE can induce adipose regeneration by regulating matrix synthesis.

External Volume Expansion Adjusted Adipose Stem Cell by Shifting the Ratio of Fibronectin to Laminin